Severe glucose deprivation causes extensive derangement of phospholipids, fatty acids and free fatty acids in cerebral cortex of rats of different ages. The hypoglycemia-induced cerebral loss of phospholipids and fatty acids persists after 60 min recovery. Changes in individual classes of lipids are largely affected by aging. In fact, during glucose deprivation and recovery, in adult animals no preferential loss of polyunsaturated fatty acids and ethanolamine phosphoglycerides occurs, suggesting that the loss could be related to oxidative rather than to peroxidative degradation. On the contrary, in senescent rats the quoted events occur, suggesting the hypothesis of a possible peroxidation of cerebral lipids. Pretreatment with some agents is performed to elucidate the aging mode of action. Papaverine (acting on macrocirculation) is uneffective, while raubasine (acting on microcirculation and metabolism) and almitrine (acting on oxygen availability) interfere with the phospholipid and fatty acid metabolism, their action being different according to the rat age.

Aging↗

PubMedDate not supplied

Influence of aging on the acute depletion of reduced glutathione induced by electrophilic agents.

A severe age-dependent depletion of reduced glutathione (GSH) occurs in rat forebrain at 1-3 h from intraperitoneal injection of the electrophilic agents cyclohexene-1-one and cycloheptene-1-one. Chronic pretreatment with central dopamine agonists (i.e., ergot alkaloids; particularly, dihydroergocriptine) partially counteracts the GSH depletion induced in 15-month-old forebrains by the prooxidants tested. In contrast, chronic pretreatment with a vasodilator agent (i.e., papaverine) magnifies the GSH depletion.

Aging↗

PubMedDate not supplied

The mitochondrial electron transfer alteration as a factor involved in the brain aging.

The tissutal concentrations of reduced glutathione (GSH) and the contents of some key components in the electron transfer chain (namely ubiquinone, cytochromes b, c1, c, and aa3) of the intraterminal mitochondria are measured in the forebrains from 20-, 60-, or 100-week-old Wistar rats. Moreover, in 60-week-old rats, the biochemical analyses are performed also 18 h after the induction of a peroxidative stress by cyclohexene-1-one. The rats have been i.p. pretreated for 8 weeks (7 days/week) with agents acting on macrocirculation (papaverine), carbohydrate metabolism (hopanthenate), lipid metabolism (phosphatidylcholine), energy transduction (theniloxazine), and dopaminergic system (dihydroergocriptine). Brain aging is characterized by the decrease in both GSH and mitochondrial cytochrome aa3, without changes in ubiquinone and cytochrome b populations. In the same way, the peroxidative stress induced by cyclohexene-1-one causes both a GSH depletion and an imbalance among the concentrations of the mitochondrial electron transfer carriers. Only cytochrome aa3 retains all the partially-reduced oxygen intermediates tightly bound to its active sites. Therefore, it is possible to hypothesize that an electron leakage at the level of the auto-oxidizing chain components (i.e., cytochrome b and ubiquinone populations) increases the release of activated oxygen species (superoxide radical, hydroxyl radical). The treatment with the quoted pharmacological tools suggests that GSH and mitochondrial electron transfer carriers are functionally linked, but not interdependent one another.

Aging↗

PubMedDate not supplied

Age-related changes by hypoxia and TRH analogue on synaptic ATPase activities.

Some synaptosomal energy-requiring ATPases were evaluated in the cerebral cortex from 3- and 24-month-old normoxic rats and rats submitted to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or TRH analogue posatireline was performed. The activities of Na+,K(+)-ATPase, low- and high-affinity Ca(2+)-ATPase, and Ca2+,Mg(2+)-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely synaptosomal plasma membranes and synaptic vesicles. With the exception of the high-affinity Ca(2+)-ATPase, aging induced a decrease in the ATPase activities from normoxic rats. The adaptation to chronic intermittent mild hypoxia was characterized by an increase in the activity of Mg(2+)-ATPase in 3-month-old rats, concomitant with a decrease in the activities of: a) Na+,K(+)-ATPase and high-affinity Ca(2+)-ATPase in both 3- and 24-month-old rats, and b) Ca2+,Mg(2+)-ATPase in 3-month-old ones. The TRH analogue posatireline increased the high-affinity Ca(2+)-ATPase in both 3- and 24-month-old hypoxic rats, concomitant with an increase in Mg(2+)-ATPase activity in 24-month-old ones. The adaptation to chronic intermittent severe hypoxia was characterized by a decrease in the activities of: a) Na+,K(+)-ATPase, Ca2+,Mg(2+)-ATPase and high-affinity Ca(2+)-ATPase in both 3- and 24-month-old rats, and b) low-affinity Ca(2+)-ATPase only in 24-month-old ones. The effect on Mg(2+)-ATPase activity was characterized by a decrease in the enzymatic form located in the synaptic plasma membranes, concomitant with an increase in the form located in the synaptic vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

PubMedDate not supplied

Are reactive oxygen species involved in Alzheimer's disease?

Alzheimer's disease has a multifactorial pathogenesis. Among the various factors involved, this review examines, in particular, the possibility of oxidative stress, meaning an imbalance between the formation and spread of reactive oxygen species (ROS) and the antioxidant defenses. This theory is supported by the following observations: (a) the alteration of mitochondrial function, which is likely to lead to the electron leakage in the respiratory chain and the consequent formation of superoxide radicals; (b) the unbalanced high activity of superoxide dismutase and monoamine oxidase B which causes the production of more H2O2; (c) the alteration of iron homeostasis which, in combination with the superoxide and H2O2, gives rise to the most deleterious hydroxyl radicals; (d) the increased lipid peroxidation and membrane alterations; (e) the pro-aggregating effect of ROS on beta/A4 protein and the C-terminal fragment of amyloid precursor (A4CT). Most of these changes are already present in the normal aging brain but are aggravated in AD presumably over a number of years. However, further investigations are needed to confirm these theories particularly regarding the alterations of another target of ROS, the proteins. Peroxidative stress is presumably present in the AD brain. This stress might not be a primary factor in the pathogenesis of AD, but a consequence of the tissue injury. In any case, it could contribute considerably to the pathology, in a vicious cycle of actions and reactions resulting in a critical mass of metabolic errors, responsible in the end for this disease.

Alzheimer Disease↗

PubMedDate not supplied

Pharmacoepidemiology of the drugs used in sports as doping agents.

Explore the source record for details and available documents.

Anabolic Agents↗

PubMedDate not supplied

Influence of aging and drug treatment on the cerebral glutathione system.

Age-related changes of the components of the glutathione system (reduced and oxidized glutathione) were evaluated in forebrains from male Wistar rats aged 5, 10, 15, 20, 25, 30 and 35 months. The trend of both forms of glutathione and the glutathione redox index markedly differs with age. Reduced glutathione increases during the first third of a rat's life and decreases thereafter. In contrast, oxidized glutathione remains relatively constant during the first half of the life-span and increases thereafter. Thus, the glutathione redox index steadily declines with age after an increase during the first third of the rat's life-span. In rats aged 10, 20 or 30 months, chronic IP treatment for two months with drugs known to modify cerebral circulation (papaverine) or the cerebral metabolism (ergot alkaloids dihydroergocristine, dihydroergocriptine) indicates that, according to the age, the cerebral glutathione system may be modified by metabolic changes rather than by circulatory events.

Aging↗

PubMedDate not supplied

Risk factors for endometrial hyperplasia: results from a case-control study.

We analyzed epidemiologic characteristics of women at risk for endometrial hyperplasia (EH), using data from a case-control study. One hundred twenty nine women aged 35-73 (median 51 years) with histologically confirmed complex endometrial hyperplasia without atypies identified at the University of Milan during the period 1990-99 were examined. Controls were 258 non hysterectomized women aged 36-74 (median 52 years), admitted to a network of hospitals covering the same area where cases had been identified for conditions other than gynecological, malignant, or hormone-related. Cases with EH were more educated than controls (OR > 12 years of education vs. < 7: 2.8, 95% CI 1.7-4.8), more frequently obese (OR 2.7, 95% CI 1.5-5.0) and diabetic (OR 2.4, 95% CI 0.8-6.9). Parous women (OR 1.8) and women reporting induced abortions (OR 1.6) showed an increased risk of EH, but the associations were not statistically significant. Compared to premenopausal women, the OR of EH was 0.2 (95% 0.1-0.5) for postmenopausal ones. Compared to women reporting menopause at age 50 or less, the OR of endometrial hyperplasia was 1.5 (95% CI 0.6-3.5) and 2.2 (95%CI 0.7-6.7), respectively, in women with menopause at age 50-52 and > or = 53. Considering postmenopausal women only the OR was 3.1 (95% CI 1.1-9.3) for use of hormonal replacement therapy (HRT). We conclude that this study indicates that high education, obesity, diabetes, and HRT use increase the risk of endometrial hyperplasia.

Adult↗

PubMedDate not supplied

The epidemiology of multiple births.

On the basis of MEDLINE and manual searches, we examined the main papers in the English literature regarding risk factors for spontaneous (i.e. not related to fertility drug use) multiple births. The constant frequency of monozygotic (MZ) pregnancies over time and in different geographical areas suggests that the determination of MZ twins is largely unchanged over time, and that a genetic mechanism may have a role. In contrast, temporal and geographical trends observed in dizygotic (DZ) pregnancies suggest that environmental factors play a role in determining this condition. At present, maternal age and hereditary components are the best-defined determinants for spontaneous multiple births.

Age Factors↗

PubMedDate not supplied

Risk factors for different histological types of ovarian cancer.

Various histological types of ovarian cancer may develop from different etiological aspects. Data separated by histological subtypes collected in the framework of a large case-control study on ovarian cancer conducted in Italy were analyzed. The cases were women below the age of 75 years, admitted to a network of hospitals in Milan. Cases were grouped into four categories by histological type: mucinous tumor (n = 52), serous tumor (n = 680), endometrioid tumor (n = 41), and other histologies including clear-cell and undifferentiated epithelial tumors (n = 50). Controls were 2758 patients admitted to the same network of hospitals for a wide spectrum of acute, nongynecological, non-hormone-related, non-neoplastic conditions. In comparison with nulliparae, the risk of serous, endometrioid, and other histologies of ovarian cancer tended to be lower in parous women, but the odds ratios (OR) were above unity for mucinous ovarian cancer. Oral contraceptive use was associated with OR lower than unity for serous (OR = 0.7) and endometrioid (OR = 0.8) ovarian cancers but not for mucinous (OR = 1.4) and other histologies (OR = 1.6). Finally, our results on dietary fat intake did not show substantial differences in all histological types of ovarian cancer.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities.

The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment.

Animals↗

PubMedDate not supplied

Reliability of the herpes simplex virus immunofluorescent test in corneal disease.

Herpetic ocular disease never produces well-identifiable morphological aspects. It is expensive, complicated and slow to culture Herpes simplex virus. The validity of the fluorescent monoclonal antibodies test was investigated using corneal cells with or without a sure herpetic lesion. The tests, on 36 cases without sure herpetic lesions, were always negative, while of the 42 patients with a clinically ascertained herpetic lesion, 38 were positive (90.5%) and 4 negative (9.5%), two of these on account of inadequate tissue preparations. Thus, this method can prove useful and reliable for diagnostic purposes.

Antibodies, Viral↗